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Endocrine-related Cancer May 2022Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs)...
Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs) represent the most recent therapeutic avenue, having raised hope with the publication of the first successful case in 2018. Here, we present an overview of immunotherapy in pituitary carcinomas and aggressive pituitary tumors, starting with the rationale for using ICIs and the implications of tumor-infiltrating lymphocytes in anterior pituitary tumors, followed by a systematic review of all published cases, analyzing both treatment response and potential predictors of response and finishing with research and clinical perspectives. Seven corticotroph and four lactotroph tumors have been so far treated with ICIs. Corticotroph tumors showed radiological partial response in 57% of cases, followed by stable disease in 29% of cases, which was accompanied by biochemical partial or complete response in 83% of cases. Half of lactotroph tumors showed radiological complete or partial response, accompanied by biochemical complete response in 33% of the cases. In the case of a dissociate response, continuation of immunotherapy combined with local treatment represents a good option. At this time, a high tumor mutational burden appears to be the most promising predictive marker of response. MMR deficiency does not guarantee a response. Negative PD-L1 staining should not preclude ICIs administration. Therefore, ICIs are a promising option after temozolomide failure. This review highlights key clinical aspects that can already be implemented into practice and also discusses tumor biology concepts and perspectives expected to improve immunotherapy outcomes.
Topics: Carcinoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Pituitary Neoplasms; Temozolomide
PubMed: 35521777
DOI: 10.1530/ERC-22-0037 -
Clinical Endocrinology Oct 2016The spectrum of pituitary stalk (PS) pathology is vast, presenting a diagnostic challenge. Published large series of PS lesions demonstrate neoplastic conditions are... (Review)
Review
The spectrum of pituitary stalk (PS) pathology is vast, presenting a diagnostic challenge. Published large series of PS lesions demonstrate neoplastic conditions are most frequent, followed by inflammatory, infectious and congenital diseases. Inflammatory pathologies however, account for the majority of PS lesions in published small case series and case reports. Physicians must be familiar with the major differential diagnoses and necessary investigations. A comprehensive history and thorough clinical examination is critical. Although magnetic resonance imaging of the PS in disease is nonspecific, associated intracranial features may narrow the differential diagnosis. Initial investigations include basic pathology and computer tomography imaging of the neck, chest, abdomen and pelvis. Further investigations should be guided by the clinical context. PS biopsy should be considered when a diagnosis is regarded essential in centres where an experienced neurosurgeon is available. Treatment is dependent on the underlying disease process and may necessitate pituitary hormone replacement.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Pituitary Diseases; Pituitary Gland; Pituitary Neoplasms
PubMed: 26950774
DOI: 10.1111/cen.13058 -
Klinicka Onkologie : Casopis Ceske a... 2017Pituitary metastases are a rare complication of generalized cancer. Metastases to the pituitary gland occur in only 1% of patients operated on for sellar tumor. The most...
BACKGROUND
Pituitary metastases are a rare complication of generalized cancer. Metastases to the pituitary gland occur in only 1% of patients operated on for sellar tumor. The most common presenting symptom in patients with pituitary metastases is diabetes insipidus, whereas this is rare in those with pituitary adenoma.
MATERIAL AND METHODS
This publication presents the cases of two patients with pituitary metastases and a systematic review of the literature. English-language publications related to pituitary metastases and published from 1957 to 2016 were identified using the PubMed database.
RESULTS
A total of 131 publications containing information about 259 patients (121 female and 138 male; mean age, 57.3 years) were identified. The most often metastasized breast carcinoma (24.6%) and lung carcinoma (23.8%), followed by thyroid carcinoma (11.3%), renal cell carcinoma (7.8%), hepatocellular carcinoma (4.3%), colorectal carcinoma (3.5%), and malignant melanoma (3.5%). The most frequent initial symptoms were manifestations of diabetes insipidus (39.6%), anterior pituitary deficiency (44.9%), perimeter disorders (51.6%), headache (37.6%), cranial nerve palsy (33.5%), and pseudoprolactinemia (16.7%). Radiotherapy (67.8%) and surgical treatment (63.9%) were the most frequently used treatment.
CONCLUSION
The average survival time from the onset of metastatic disease was 11.8 months. Surgical therapy alone or in combination with radiation therapy does not prolong survival, but alleviates symptoms and improves quality of life.Key words: pituitary metastasis - diabetes insipidus - hypopituitarism - transsphenoidal surgery The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 1. 2017Accepted: 4. 4. 2017.
Topics: Cranial Nerve Diseases; Diabetes Insipidus; Female; Humans; Male; Middle Aged; Pituitary Diseases; Pituitary Neoplasms; Quality of Life
PubMed: 28832172
DOI: 10.14735/amko2017273 -
American Journal of Otolaryngology 2022The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with... (Review)
Review
OBJECTIVE
The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management.
METHODS
A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded.
RESULTS
282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints.
CONCLUSION
LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.
Topics: Amyloidosis; Hoarseness; Humans; Laryngeal Diseases; Larynx; Vocal Cords
PubMed: 35917657
DOI: 10.1016/j.amjoto.2022.103550 -
Neurosurgery Aug 2016The prevalence of hypothalamic-pituitary dysfunction after aneurysmal subarachnoid hemorrhage has not been precisely determined, and conflicting results have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of hypothalamic-pituitary dysfunction after aneurysmal subarachnoid hemorrhage has not been precisely determined, and conflicting results have been reported in the literature.
OBJECTIVE
To perform a systematic review and meta-analysis investigating the prevalence of pituitary insufficiency after aneurysmal subarachnoid hemorrhage and to focus on basal serum and dynamic test differences.
METHODS
The prevalence of pituitary dysfunction was quantified at 3 to 6 months and >6 months after aneurysmal subarachnoid hemorrhage. Proportions were transformed with the logit transformation. A subgroup analysis was performed focusing on the differences in outcome between basal serum and dynamic tests for the diagnosis of growth hormone deficiency (GHD) and secondary adrenal insufficiency.
RESULTS
Overall prevalence of hypopituitarism differed considerably between studies, ranging from 0.05 to 0.45 in studies performed between 3 and 6 months after the event and from 0 to 0.55 in long-term studies (>6 months), with pooled frequencies of 0.31 (95% confidence interval [CI]: 0.22-0.43) and 0.25 (95% CI: 0.16-0.36), respectively. Pooled frequency of GHD at 3 to 6 months was 0.14 (95% CI: 0.08-0.24). At >6 months, GHD prevalence was 0.19 (95% CI: 0.13-0.26) overall, but ranged from 0.15 (95% CI: 0.06-0.33) with the insulin tolerance test to 0.25 (95% CI: 0.15-0.36) using the growth hormone releasing hormone + arginine test.
CONCLUSION
Hypopituitarism is a common complication in patients with aneurysmal subarachnoid hemorrhage, with GHD being the most prevalent diagnosis. We showed that variations in prevalence rates in the literature are partly due to methodological differences among pituitary function tests.
ABBREVIATIONS
ACTH, adrenocorticotropic hormoneaSAH, aneurysmal subarachnoid hemorrhageGHD, growth hormone deficiencyGHRH, growth hormone-releasing hormoneGST, glucagon stimulation testIGF, insulin-like growth factor 1ITT, insulin tolerance testSAH, subarachnoid hemorrhage.
Topics: Humans; Hypopituitarism; Prevalence; Subarachnoid Hemorrhage
PubMed: 26645970
DOI: 10.1227/NEU.0000000000001157 -
Acta Endocrinologica (Bucharest,... 2023Pituitary adenomas are benign tumors, usually found in men in their 3 and 5 decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations...
CONTEXT
Pituitary adenomas are benign tumors, usually found in men in their 3 and 5 decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment.
OBJECTIVE
This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions.
DESIGN
This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach.
SUBJECTS AND METHODS
We performed an advanced search on Web of Science and PubMed databases on October 10, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria's, 19 studies were fully read and analyzed.
RESULTS
Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential.
CONCLUSIONS
For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they're cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined "above and below" simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage.
PubMed: 37908878
DOI: 10.4183/aeb.2023.228 -
Pituitary Oct 2023Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
PURPOSE
Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
METHODS
We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas.
RESULTS
Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14).
CONCLUSION
Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.
Topics: Humans; Pituitary Neoplasms; Neoplasm Recurrence, Local; Adenoma; ACTH-Secreting Pituitary Adenoma; Pituitary Gland
PubMed: 37523025
DOI: 10.1007/s11102-023-01341-4 -
Journal of Child and Adolescent... Sep 2022Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore aimed to assess the effects of antipsychotics on prolactin levels and associated somatic ARs in children and adolescents. We systematically searched PubMed and CENTRAL for placebo-controlled randomized trials of antipsychotics in children and adolescents aged ≤18 years, reporting prolactin levels and related ARs. We conducted a random-effect meta-analysis and assessed risk of bias version 2 (ROB2). Thirty-two randomized controlled trials with an average trial duration of 6 weeks, covering 4643 participants with an average age of 13 years and a male majority of 65.3%. Risk of bias across domains was low or unclear. The following antipsychotic compounds: aripiprazole ( = 810), asenapine ( = 506), lurasidone ( = 314), olanzapine ( = 179), paliperidone ( = 149), quetiapine ( = 381), risperidone ( = 609), and ziprasidone ( = 16) were compared with placebo ( = 1658). Compared with placebo, statistically significant higher prolactin increase occurred with risperidone (mean difference [MD] = 28.24 ng/mL), paliperidone (20.98 ng/mL), and olanzapine (11.34 ng/mL). Aripiprazole significantly decreased prolactin (MD = -4.91 ng/mL), whereas quetiapine, lurasidone, and asenapine were not associated with significantly different prolactin levels than placebo. Our results on ziprasidone are based on a single study, making it insufficient to draw strong conclusions. On average, 20.8% of patients treated with antipsychotic developed levels of prolactin that were too high (hyperprolactinemia), whereas only 1.03% of patients reported prolactin-related ARs. Data were highly limited for long-term effects. In children and adolescents, risperidone, paliperidone, and olanzapine are associated with significant prolactin increase, whereas aripiprazole is associated with significant decrease. Despite the significant changes in prolactin level, few ARs were reported. Study protocol on PROSPERO: CRD42018116451.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Dibenzocycloheptenes; Humans; Hyperprolactinemia; Lurasidone Hydrochloride; Male; Olanzapine; Paliperidone Palmitate; Piperazines; Prolactin; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles
PubMed: 36074098
DOI: 10.1089/cap.2021.0140 -
Frontiers in Endocrinology 2016PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA),... (Review)
Review
PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing's syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.
PubMed: 26869991
DOI: 10.3389/fendo.2016.00001 -
Journal of Clinical Medicine Mar 2022: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and...
: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing's disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. : The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, = NS) and Cushingoid features (27.5% vs. 20.0%, = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.
PubMed: 35329884
DOI: 10.3390/jcm11061558